Brain-derived Neurotrophic Factor Genetic Polymorphism Research Articles

Brain-derived neurotrophic factor genetic polymorphism rs6265 and creativity.

The protein brain-derived neurotrophic factor (BDNF) promotes neural plasticity of the central nervous system and plays an important role for learning and memory. A single nucleotide polymorphism (rs6265) at position 66 in the pro-region of the human BDNF gene, resulting in a substitution of the amino acid valine (val) with methionine (met), leads to attenuated BDNF secretion and has been associated with reduced neurocognitive function. Inhomogeneous results have been found regarding the effect of the BDNF genotype on behavior. We determined the BDNF genotype and performance on the Compound Remote Associate (CRA) task as a common measure of creativity in 76 healthy university students. In our main analyses, we did not find significant differences between met-carriers (n = 30) and non-met carriers (n = 46). In a secondary analysis, we found that met-carriers had a slower solution time (medium effect size) for items of medium difficulty. Our results suggest that met-carriers and non-met-carriers do not generally differ regarding their creativity, but non-met-carriers may have a certain advantage when it comes to moderately difficult problems. The wider literature suggests that both genetic variants come with advantages and disadvantages. Future research needs to sharpen our understanding of the disadvantages and, potentially, advantages met allele carriers may have.

Impact of brain-derived neurotrophic factor genetic polymorphism on cognition: A systematic review.

IntroductionBrain‐derived neurotrophic factor (BDNF) has an important role in the neurogenesis and neuroplasticity of the brain. This systematic review was designed to examine the association between BDNF Val66Met (rs6265) polymorphism and four cognitive domains—attention and concentration, executive function, verbal fluency, and memory, respectively.MethodologyPrimary literature search was performed using search engines such as PubMed and Scopus. Observational studies that evaluated the neurocognitive performances in relation to BDNF polymorphism within human subjects were included in this review, while animal studies, overlapping studies, and meta‐analysis were excluded.ResultsForty of 82 reviewed studies (48.8%) reported an association between Val66Met polymorphism and neurocognitive domains. The proportion of the studies showing positive findings in cognitive performances between Val/Val homozygotes and Met carriers was comparable, at 30.5% and 18.3%, respectively. The highest percentage of positive association between Val66Met polymorphism and neurocognition was reported under the memory domain, with 26 of 63 studies (41.3%), followed by 18 of 47 studies (38.3%) under the executive function domain and four of 23 studies (17.4%) under the attention and concentration domain. There were no studies showing an association between Val66Met polymorphism and verbal fluency. In particular, Val/Val homozygotes performed better in tasks related to the memory domain, while Met carriers performed better in terms of executive function, in both healthy individuals and clinical populations.ConclusionWhile numerous studies report an association between Val66Met polymorphism and neurocognitive changes in executive function and memory domains, the effect of Met allele has not been clearly established.

Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer.

BackgroundBrain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment.MethodsOverall, 145 patients receiving chemotherapy for early-stage breast cancer (mean age: 50.8 ± 8.8 y; 82.1% Chinese) were recruited. Patients' cognitive functions were assessed longitudinally using the validated Functional Assessment of Cancer Therapy–Cognitive Function (v.3) and an objective computerized tool, Headminder. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition after adjusting for ethnicity and clinically important covariates.ResultsOf the 145 patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met genotype was associated with statistically significant lower odds of developing cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08–0.92; P = .036). The Met carriers were less likely to experience impairment in the domains of verbal fluency (OR = 0.34; 95% CI: 0.12–0.90; P = .031) and multitasking ability (OR = 0.37; 95% CI: 0.15–0.91; P = .030) compared with the Val/Val homozygote. No associations were observed between Headminder and the BDNF Val66Met polymorphism.ConclusionsThis is the first study to provide evidence that carriers of the BDNF Met allele are protected against chemotherapy-associated cognitive impairment. Further studies are required to validate the findings.

Association between brain-derived neurotrophic factor genetic polymorphism Val66Met and susceptibility to bipolar disorder: a meta-analysis.

BackgroundIn view of previous conflicting findings, this meta-analysis was performed to comprehensively determine the overall strength of associations between brain-derived neurotrophic factor (BDNF) genetic polymorphism Val66Met and susceptibility to bipolar disorders (BPD).MethodsLiteratures published and cited in Pubmed and Wanfang Data was searched with terms of ‘Val66Met’, ‘G196A’, ‘rs6265’, ‘BDNF’, ‘association’, and ‘bipolar disorder’ up to March 2014. All original case–control association studies were meta-analyzed with a pooled OR to estimate the risk and 95% confidence interval (CI) to reflect the magnitude of variance.ResultsTwenty-one case–control association studies met our criteria for the meta-analysis. Overall, there was no significant difference in allelic distribution of Val66Met polymorphism between patients and controls with a pooled OR = 1.03 (95% CI 0.98, 1.08) although there was a trend towards association between Val66Met polymorphism and BPD in Caucasians with an OR of 1.08 (95% CI 1.00, 1.16). However, subgroup analyses showed that there was a significant association of Val allele with decreased disease susceptibility for bipolar disorder type II with a pooled OR of 0.88 (95% CI 0.78, 0.99).ConclusionsThere is no compelling evidence to supportVal66Met polymorphism in BDNF gene playing an important role in the susceptibility to BPD across different ethnicities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0366-9) contains supplementary material, which is available to authorized users.

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Right Prefrontal Cortex Combined With Partial Sleep Deprivation in Treatment-Resistant Depression

Sham-controlled low-frequency repetitive transcranial magnetic stimulation (rTMS) was used in patients with pharmacoresistant major depression as an added treatment along with partial sleep deprivation (PSD). In addition, the potential predictive role of brain-derived neurotrophic factor genetic polymorphism on treatment response was analyzed. We recruited 19 female patients (48.3 ± 8.6 years old) with treatment-resistant unipolar major depression (Hamilton Depression Rating Scale [HDRS] score ≥20) who were on a stable antidepressant treatment. They received either 1-Hz rTMS or sham stimulation over the right dorsolateral prefrontal cortex (intensity of 110% of the threshold; 3000 stimuli per protocol; and 10 daily sessions). Additionally, PSD was applied once per week during the treatment. The patients were evaluated (HDRS and Clinical Global Impression Scale) by a blind rater at baseline (B) and after 2 and 3 weeks (W2 and W3) of treatment for short-term outcome. Long-term evaluations were performed after 12 (W12) and 24 weeks (W24) for patients who received active stimulation. Eleven patients in the active group showed a significant HDRS score reduction from 30.09 ± 3.53 (B) to 16.73 ± 5.71 (W3) compared to the lack of therapeutic response in the sham-treated patients. The long-term follow-up for the active group included 64% of the responders at W12 and 55% at W24. Full remission (HDRS ≤10) was achieved in 5 of 11 patients. Four of these 5 patients with long-term sustained remission expressed the Val66Val genotype. Our study suggests a clinically relevant response, persisting for up to 6 months, from 1-Hz rTMS over the right dorsolateral prefrontal cortex and PSD in patients with pharmacoresistant major depression. The brain-derived neurotrophic factor Val66Val homozygous genotype may be related to a better treatment outcome.

Is mania caused by overactivity of central brain-derived neurotrophic factor?

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, can modulate synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems, as well as the intracellular signal-transduction pathway. Recent studies had demonstrated that BDNF may play a role in the antidepressant mechanism and the pathogenesis of major depression. These findings implicated that BDNF may involve in mood regulation. In addition, (1) studies found positive association between BDNF genetic polymorphism and bipolar affective disorders; (2) agents which potentially induce manic states also increase BDNF, and (3) increase in mossy fibers were noted for bipolar affective disorder brain and BDNF is related to the induction of aberrant mossy fiber sprouting. From these finding, it is proposed that BDNF overactivity may be implicated in the manic state. The notion of BDNF overactivity in mania suggests that factors associated with increased BDNF activity may proffer the etiological fundamentals for bipolar affective disorder. Further, exploration of this hypothesis can provide a new direction in the treatment of the bipolar affective disorder.